The relationship between pain responses and stimulus strength is often predictable. For a patient with facial nerve damage, a light touch on the face can cause an excruciating pain (trigeminal neuralgia). An amputee may complain of constant pain or a tingling sensation in a part of a limb that is no longer there (phantom limb pain) Lesions of the nervous system as a result of an operation or disease often produce pain which is sustained long after the original injury is healed (neuropathic pain). Although all these disorders are triggered by injuries to the nerve, we do not know how pain sustains itself. One possibility for this to occur is that pain transmission neurons, such as spinothalamic tract and trigeminothalamic tract cells, become chronically active after being intensively stimulated during injury. We propose here a mechanism that can bring about sustained excitation of projection neurons. In this proposal, experiments are designed to test this hypothesis. The responses to excitatory amino acids and peptides will be measured using patch clamp method. The preparations used include identified neurons isolated from spinal trigeminal subnucleus caudalis and the same type of neurons located in thin medulla slices. Understanding the mechanism underlying chronic pain will provide us with valuable clues about pain mechanism in general. More importantly, the information can easily translate into better therapy for patients in pain.